EPI-743 for Mitochondrial Respiratory Chain Diseases

Inclusion criteria:

1. Patients with genetic diagnosis: Genetically confirmed diagnosis of Inherited
mitochondrial respiratory chain disease

2. Patients with clinical diagnosis: Diagnosis of inherited mitochondrial disease absent
genetic confirmation; Specifically, subjects must meet the diagnostic criteria of
"definite" or "probable" mitochondrial disease as defined by Bernier et al., 2002

3. Deemed by principal investigator to be within 90 days of end-of-life hospice/terminal
care

4. Male or female age > one year

5. Hematocrit within normal range for age group

6. Agreement to use contraception if within reproductive years

7. Patient or patient's guardian able to consent and comply with protocol requirements

8. Presence of caregiver to ensure study compliance

9. Abstention from use of all pill-form dietary supplements and non-prescribed
medications (except as allowed by the investigator)

10. Abstention from foods or beverages or bars fortified with Coenzyme Q10, vitamin E,
super-fortified "functional" foods or beverages

11. Abstention from use of idebenone

12. Clinically staged with a Mitochondrial Disease Scale such as the Newcastle Score

Exclusion criteria:

1. Allergy to EPI-743, vitamin E or sesame oil

2. Clinical history of bleeding or abnormal PT/PTT (excluding anticoagulation Rx)

3. Hepatic insufficiency with LFTs greater than two times normal

4. Renal insufficiency requiring dialysis

5. Fat malabsorption syndromes precluding drug absorption

6. Any other concurrent inborn errors of metabolism

7. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in
lactic acidosis

8. Pregnancy